Summary of project PR001846

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001846. The data can be accessed directly via it's Project DOI: 10.21228/M83H81 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001846
Project DOI:doi: 10.21228/M83H81
Project Title:Lipidomics study of FASN inhibition in HT-29 and HCT 116 spheroids
Project Type:MS Quantitative Analysis
Project Summary:Cancerous cells synthesize most of their lipids de novo to keep up with their rapid growth and proliferation. Fatty acid synthase (FAS) is a key enzyme in the lipogenesis pathway that is upregulated in many cancers and has gained popularity as a druggable target of interest for cancer treatment. The first FAS inhibitor discovered, cerulenin, initially showed promise for chemotherapeutic purposes until it was observed that it had adverse side effects in mice. TVB2640 (Denifanstat), is part of the newer generation of inhibitors. With multiple generations of FAS inhibitors being developed, it is vital to understand their distinct molecular downstream effects to elucidate potential interactions in the clinic. Here, we profile the lipidome of two different colorectal cancer (CRC) spheroids treated with a generation 1 inhibitor (cerulenin) or a generation 2 inhibitor (TVB-2640). We observe that the cerulenin causes drastic changes to the spheroid morphology as well as alterations to the lipid droplets found within CRC spheroids. TVB-2640 causes higher abundances of polyunsaturated fatty acids (PUFAs) whereas cerulenin causes decreased abundance of PUFAs. The increase in PUFAs in TVB-2640 exposed spheroids indicates it is causing cells to die via a ferroptotic mechanism rather than a conventional apoptotic or necrotic mechanism.
Institute:The Ohio State University
Department:Chemistry and Biochemistry
Laboratory:Amanda Hummon Lab
Last Name:Fries
First Name:Brian
Address:460 W 12th Ave, 470, Columbus, Ohio, 43210, USA
Email:fries.94@osu.edu
Phone:9375221195

Summary of all studies in project PR001846

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
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(* : Contains raw data)
ST002967 Lipidomics study of FASN inhibition in HT-29 and HCT 116 spheroids Homo sapiens The Ohio State University MS 2024-04-02 1 38 Uploaded data (29.2G)*
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